Thursday, December 22, 2016

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

Public Release: 21-Dec-2016

UTHealth research could lead to blood test to detect Creutzfeldt-Jakob disease

University of Texas Health Science Center at Houston

HOUSTON - (Dec. 21, 2016) - The detection of prions in the blood of patients with variant Creutzfeldt-Jakob disease could lead to a noninvasive diagnosis prior to symptoms and a way to identify prion contamination of the donated blood supply, according to researchers at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth).

The results of the research, led by senior author Claudio Soto, M.D., professor in the Department of Neurology and the director of the George and Cynthia Mitchell Center for Alzheimer's disease and Related Brain Disorders at UTHealth, were published today in Science Translational Medicine, a journal of the American Association for the Advancement of Science. First author of the paper is Luis Concha-Marambio, senior research assistant in the Department of Neurology at McGovern Medical School.

" Our findings, which need to be confirmed in further studies, suggest that our method of detection could be useful for the noninvasive diagnosis of this disease in pre-symptomatic individuals," Soto said. "Early diagnosis would allow any potential therapy to be given before substantial brain damage has occurred. In the case of the blood supply, availability of a procedure to efficiently detect small quantities of the infectious agent would allow removal of blood units contaminated with prions, so that new cases can be minimized substantially."

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant Creutzfeldt-Jakob disease (vCJD), which is caused by the transmission of bovine spongiform encephalopathy - commonly known as mad cow disease - from infected cattle to humans.

Since 1990, 178 people in the United Kingdom have died from vCJD, according to the National CJD Research & Surveillance Unit at the University of Edinburgh. The disease has claimed an additional 49 people worldwide, including four United States residents, according to the European Centre for Disease Prevention and Control. In a handful of cases, the disease was spread through the donated blood supply.

The disease can lay silent in the body for decades as damage slowly builds in the brain from the misfolded infectious proteins called prions. On average, people infected with vCJD die two years after the development of the first symptoms, which can include psychiatric alterations such as depression, anxiety and hallucinations that progress to more severe dementia, muscle contractions and loss of coordination.

Soto's team analyzed blood samples from 14 cases of vCJD and 153 controls, which included patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. To detect the prions, the team used a protein misfolding cyclic amplification assay, invented in Soto's lab, which mimics the prion replication process in vitro that occurs in prion disease.

The results showed that prions could be detected with 100 percent sensitivity and specificity in blood samples from vCJD patients.

The new study builds on years of research by Soto's team, whose detection of prions in urine was published in the New England Journal of Medicine in August 2014. In June of this year, Soto received $11 million from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to study the pathogenesis, transmission and detection of prion diseases including chronic wasting disease in deer.

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Soto is also on the faculty and Concha-Marambio is a student at The University of Texas Graduate School of Biomedical Sciences at Houston.

Co-authors are Sandra Pritzkow, Ph.D., from McGovern Medical School; Paul Schulz, M.D., professor of neurology from McGovern Medical School and Memorial Hermann Mischer Neuroscience Institute at the Texas Medical Center; Fabio Moda, Ph.D., and Fabrizio Tagliavini, M.D., from Istituto Neurologico Carlo Besta in Milan; and James W. Ironside, FMedSci, FRSE, professor of clinical neuropathology at the National CJD Research and Surveillance Unit at the University of Edinburgh.

The research was supported by grants from the National Institutes of Health (P01AI106705, R42NS079060, R01NS049173).

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A new blood test for prion diseases

Prions are the proteinaceous infectious agents responsible for various animal and human diseases. The transmission of bovine spongiform encephalopathy into humans has led to a new illness, termed variant Creutzfeldt-Jakob disease (vCJD). Currently, the number of people infected by this new disease is unknown, which is a major concern because it has been shown that preclinical carriers of vCJD prions can transmit the disease by blood transfusion. Now, Concha-Marambio et al. report the development of a biochemical test to detect vCJD prions in blood with 100% sensitivity and specificity. Availability of a highly efficient blood test for vCJD is important to minimize further transmission of the disease, to increase blood safety, and to allow early diagnosis of this disease.

Abstract

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrPSc) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrPSc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrPSc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology.

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My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS